Niobium carbide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-10-08 to 2014-02-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

no guideline available

Deviations:

not applicable

Principles of method if other than guideline:

This report measured bioaccessibility of Niobium carbide in body fluid simulants as a surrogate for bioavailability.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Niobium carbide

EC Number:

235-117-8

EC Name:

Niobium carbide

Cas Number:

12069-94-2

Molecular formula:

CNb

IUPAC Name:

niobium(4+) methanetetraide

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Niobium Carbide
- Purity: 88.6 % niobium

Radiolabelling:

no

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not applicable

Administration / exposure

Route of administration:

other: in vitro study

Vehicle:

other: not applicable

Details on exposure:

Not applicable

Duration and frequency of treatment / exposure:

Not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
0.1 g of test substance in 50 mL of simulated fluid

No. of animals per sex per dose / concentration:

Not applicable

Control animals:

other: not applicable

Positive control reference chemical:

Not applicable

Details on study design:

Niobium carbide was extracted in leaching fluids for two time points: 2 hrs and 24 hrs. The extractions were performed using 0.1 gram of sample in 50 mL of simulated fluid. A shaker water bath at a temperature of 37± 2°C was used. All extractions were performed in duplicate. The extracts were analyzed for soluble niobium using EPA Method #200.8 (ICP/MS). Results were reported as µg Nb/g sample and as % Nb release/Nb content.

Details on dosing and sampling:

Not applicable

Statistics:

Not applicable

Results and discussion

Preliminary studies:

Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not applicable

Details on distribution in tissues:

Not applicable

Details on excretion:

Not applicable

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Not applicable

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

see below (Table 1-5)

Any other information on results incl. tables

Table 1: Soluble Niobium in Simulated Gastric fluid

Extraction time	Weight used (g)	µg Niobium/g sample	% Niobium release/Niobium content
2 hours	0.1002	<25.0	-
(dup)	0.1007	<25.0	-
24 hours	0.1005	<25.0	-
(dup)	0.1008	<25.0	-

Table 2: Soluble Niobium in Simulated Interstitial fluid

Extraction time	Weight used (g)	µg Niobium/g sample	% Niobium release/Niobium content
2 hours	0.1015	74.0	0.01
(dup)	0.1008	66.0	0.01
24 hours	0.1019	206	0.02
(dup)	0.1021	181	0.02

Table 3:Soluble Niobium in Simulated Lysosomal fluid

Extraction time	Weight used (g)	µg Niobium/g sample	% Niobium release/Niobium content
2 hours	0.1003	45.0	0.01
(dup)	0.1009	59.0	0.01
24 hours	0.1040	317	0.04
(dup)	0.1033	319	0.04

Table 4: Artificial Perspiration

Extraction time	Weight used (g)	µg Niobium/g sample	% Niobium release/Niobium content
2 hours	0.1003	30.0	0.003
(dup)	0.1009	30.0	0.003
24 hours	0.1001	105	0.01
(dup)	0.1000	110	0.01

Table 5: PBS

Extraction time	Weight used (g)	µg Niobium/g sample	% Niobium release/Niobium content
2 hours	0.1002	<25.0	-
(dup)	0.1005	<25.0	-
24 hours	0.1004	<25.0	-
(dup)	0.1001	<25.0	-

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
The release of niobium ions from niobium carbide is very low in artificial body fluids. In simulated gastric fluid the release of niobium ions was below the detection limit. In simulated interstitial fluid 0.02% niobium was released after 24 hours. In simulated lysosomal fluid 0.04% niobium was released after 24 hours. In artificial perspiration 0.01% niobium was released after 24 hours. In phosphate buffered saline the release of niobium ions was below the detection limit.

Executive summary:

This report measured bioaccessibility of niobium carbide as a surrogate for bioavailability. Soluble niobium was measured using the EPA method #200.8 (ICP/MS) after incubation of niobium carbide in simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, artificial perspiration, and PBS). Results were reported as µg Nb/g sample and as %Nb release/Nb content. The amount of dissolved niobium given as µg Nb/g sample and % Nb release/Nb content are summarized in the table below (mean values of the duplicates):

Simulated Body Fluid	pH	Extraction Time	µg Nb/ g sample	% Nb release/ Nb content
Gastric fluid	pH 1.5	2 h	<25.0	BDL
		24 h	<25.0	BDL
Intersitital fluid	pH 7.4± 0.2	2 h	70.0	0.01
		24 h	194	0.02
Lysosomal fluid	pH 4.5-5.0	2 h	52	0.01
		24 h	318	0.04
Artificial Perspiration	pH 6.5 ± 0.1	2 h	30	0.003
		24 h	108	0.01

BDL: Below detection limit. Based on the results, the bioavailability of niobium carbide would be expected to be very low for all routes of administration.